Alterations in apoptosis and epithelial-mesenchymal transformation in an in vitro cleft palate model.

The processes of apoptosis and epithelial-mesenchymal transformation have been identified as two major mechanisms by which secondary palatal shelves achieve fusion. The aim of this study was to investigate alterations in these mechanisms by changing the physical distance between paired palatal shelves in an in vitro model of palatogenesis. Wild-type palatal pairs were dissected from E13.5 CD1 mouse embryos and allowed to grow in tissue culture for 48 hours at various intershelf distances. During the fusion process, medial edge epithelial cell fate was assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, to evaluate apoptosis, and carboxyfluorescence (carboxy-2,7'-dichlorofluorescein diacetate succinimidyl ester) labeling, to measure transformation to mesenchymal cells. Palatal pairs separated in culture greater than or equal to 0.4 mm failed to fuse. TUNEL staining showed that the number of apoptotic cells in the palatal shelves increased as the intershelf distance increased, becoming marked in shelves that did not achieve fusion. The amount of epithelial-mesenchymal transformation, however, decreased with increasing intershelf distance. These results suggest that the contribution of epithelial-mesenchymal transformation and apoptosis to palatal shelf development and fusion can be altered by physical proximity. Therefore, one mechanism behind clefting in utero may result from an imbalance in epithelial-mesenchymal transformation and apoptosis as observed in vitro where palatal shelves are challenged to fuse by physical separation. This effect could be significant in the understanding and treatment of developmental palatal abnormalities. Perhaps in utero manipulation of intershelf spacing or epithelial-mesenchymal transformation and/or apoptosis could reverse the clefting paradigm.

A cluster of tuberculosis associated with use of a marijuana water pipe.

SETTING: New cases of pulmonary tuberculosis (TB) were noted in a cluster of young Caucasian males, an unusual ethnic group for this disease in Queensland, Australia. It was noted that marijuana water pipe ('bong') smoking was common amongst cases and contacts. OBJECTIVE: To report this cluster of TB and to investigate whether shared use of a marijuana water pipe was associated with transmission of TB. DESIGN: All contacts were identified and screened according to standard protocols. Cases were asked to list contacts with whom they had shared a marijuana water pipe. RESULTS: Five cases of open pulmonary TB were identified clinically and on sputum culture, and all isolates of Mycobacterium tuberculosis were identical on typing. Of 149 contacts identified, 114 (77%) completed screening, and 57 (50%) had significant tuberculin skin test (TST) reactions on follow-up. Of 45 contacts who had shared a marijuana water pipe with a case, 29 (64%) had a significant TST reaction. CONCLUSION: Sharing a marijuana water pipe with a case of pulmonary TB was associated with transmission of TB (OR 2.22, 95 % CI 0.96-5.17), although the most important risk factor for acquiring TB infection in this cluster was close household contact with a case (OR 4.91, 95% CI 1.13-20.70).

The influence of human immunodeficiency virus infection and intravenous drug abuse on complications of hemodialysis access surgery.

To examine the influence of human immunodeficiency virus (HIV) infection on complications in dialysis access surgery, a review was performed on patients undergoing hemodialysis at two major metropolitan medical centers over a 30-month period. One hundred eight patients underwent a total of 169 graft procedures; mean follow-up was 14 1/2 months. There were 18 (17%) patients who were HIV-positive who had no symptoms, 11 (10%) patients with acquired immunodeficiency syndrome (AIDS), and 79 (73%) patients who were HIV-negative. Twenty-three percent (25/108) of patients had a history of intravenous drug abuse (IVDA), most of whom also had either AIDS or asymptomatic HIV infection. Dialysis procedures included 44 autogenous reconstructions (26%), 117 polytetrafluoroethylene (PTFE) grafts (69%), and 8 (5%) procedures of unknown type. Arteriovenous fistula or graft thrombosis was a frequent complication. The overall 12-month graft patency rate was 41%, and patients with HIV infection or a history of IVDA did not have a significantly increased risk of thrombosis. Multivariate analysis showed that the use of PTFE as opposed to autogenous reconstruction was the only significant risk factor found for occlusion within the first 12 months after operation (p < 0.01). Twenty-five graft infections occurred, all in PTFE grafts. The PTFE graft infection rate was 43% in patients with AIDS, 36% in patients who were HIV-positive and who had no symptoms, and 15% in patients who were HIV-negative (p < 0.05). Patients with a history of IVDA had a 41% PTFE graft infection rate versus a 13% infection rate in patients who did not have a history of IVDA (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Are condom instructions readable? Results of a readability study.

The use of condoms has assumed a central position in the current strategy to prevent sexual transmission of the human immunodeficiency virus. The effectiveness of condoms in disease prophylaxis is dependent, to a degree, on their correct use. Condom manufacturers routinely include information on condom use either printed on the actual package or in an enclosed package insert. With the use of three readability formulas, the reading grade level was determined for 14 different sets of instructions included with 25 brands of condoms manufactured by 7 domestic and 1 overseas manufacturer. The readability formulas, when applied to instructions for condom use, estimated that, conservatively, 8 of the 14 instructions required at least reading at the level of a high school graduate and none required less than a 10th grade level. Clearly written instructions and simple concepts could assist current and future condom users in the correct use of condoms and improve the effectiveness of condoms in the prevention of AIDS and other sexually transmitted diseases.

Molecular cloning and sequence of a cholesterol-repressible enzyme related to prenyltransferase in the isoprene biosynthetic pathway.

Differential hybridization and molecular cloning have been used to isolate CR39, a cDNA which hybridizes to a 1.2-kilobase (kb) mRNA in rat liver. The level of CR39 mRNA was increased seven- to ninefold over normal levels by dietary cholestyramine and mevinolin and decreased about fourfold compared with normal levels by cholesterol feeding or administration of mevalonate. Similar changes in the mRNA levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and HMG-CoA synthase were observed under the various conditions. In vitro translation of either CR39 hybrid selected RNA or 1.2-kb CR39 RNA generated by an SP6 in vitro transcription system produced a polypeptide of 39,000 daltons. As deduced from the nucleotide sequence of a full-length CR39 cDNA, the rat CR39 polypeptide contained 344 amino acids and had a molecular weight of 39,615. The predicted amino acid composition and submit molecular weight of the rat CR39 were very similar to those of prenyltransferases isolated from chicken, pig, and human. The sequence of amino acid residues 173 through 203 in the rat CR39 polypeptide showed that 17 out of 30 matched an active-site peptide of avian liver prenyltransferase. Thus, alterations in the rate of cholesterogenesis resulted in the coordinate regulation of three mRNAs encoding HMG-CoA reductase, HMG-CoA synthase, and CR39, the latter being tentatively identified as prenyltransferase.